{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:26:51Z","timestamp":1789183611329,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union through the European Social Fund under the Operational Programme Knowledge Education Development 2014\u20132020","award":["POWR.03.02.00-00-I014\/17-00"],"award-info":[{"award-number":["POWR.03.02.00-00-I014\/17-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>For the first time, adventitious and hairy root cultures of Salvia apiana (white sage) have been established and analyzed for the content of secondary metabolites. Non-transformed roots derived from sterile seedlings were maintained on a full-strength IBA-supplemented SH medium. Adventitious roots yielded up to 44.5 mg\/g and 18.7 mg\/g DW rosmarinic acid when grown in shake flasks and immersion-column bioreactors, respectively. Transformed root cultures were established from S. apiana microshoots, infected with A4 and LBA9402 strains of Rhizobium rhizogenes. The obtained hairy root cultures (three and two clonal lines established using A4 and LBA9402 strains, respectively) were maintained in the PGR-free, full-strength SH medium. The most productive root line, established using A4 strain, accumulated rosmarinic acid at 38.1 and 39.6 mg\/g DW when grown in shake flasks and spray bioreactors, respectively. Neither adventitious nor transformed roots of S. apiana produced diterpenoids, identified in roots of the field-grown plants, and instead proved to be a selective source of rosmarinic acid.<\/jats:p>","DOI":"10.3390\/ijms26073138","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"3138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Adventitious and Hairy Root Cultures of Salvia apiana as a Source of Rosmarinic Acid"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8929-2999","authenticated-orcid":false,"given":"Agata","family":"Krol","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, Genera\u0142a J\u00f3zefa Hallera Street 107, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kokotkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, Genera\u0142a J\u00f3zefa Hallera Street 107, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-283X","authenticated-orcid":false,"given":"Aleksandra","family":"Krolicka","sequence":"additional","affiliation":[{"name":"Laboratory of Biologically Active Compounds, Intercollegiate Faculty of Biotechnology UG and MUG, University of Gdansk, Abrahama Street 58, 80-307 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-7852","authenticated-orcid":false,"given":"Krzysztof","family":"Hinc","sequence":"additional","affiliation":[{"name":"Division of Molecular Bacteriology, Medical University of Gdansk, D\u0119binki Street 1, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-8231","authenticated-orcid":false,"given":"Anna","family":"Badura","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiellonska Street 15, 85-067 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1474-7864","authenticated-orcid":false,"given":"Andzelika","family":"Lorenc","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiellonska Street 15, 85-067 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4189-6451","authenticated-orcid":false,"given":"Urszula","family":"Marzec-Wroblewska","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiellonska Street 15, 85-067 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Bucinski","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiellonska Street 15, 85-067 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-1346","authenticated-orcid":false,"given":"Lukasz","family":"Kuzma","sequence":"additional","affiliation":[{"name":"Department of Biology and Pharmaceutical Botany, Medical University of Lodz, 1 Muszy\u0144skiego Street, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Luczkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, Genera\u0142a J\u00f3zefa Hallera Street 107, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S1572-5995(08)80017-8","article-title":"Bioactive Diterpenoids of Salvia Species","volume":"35","author":"Kabouche","year":"2008","journal-title":"Stud. Nat. Prod. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s11101-019-09633-z","article-title":"Quinone Diterpenes from Salvia Species: Chemistry, Botany, and Biological Activity","volume":"18","author":"Bisio","year":"2019","journal-title":"Phytochem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0031-9422(01)00415-0","article-title":"Polyphenolics of Salvia\u2014A Review","volume":"59","author":"Lu","year":"2002","journal-title":"Phytochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13020-024-00971-5","article-title":"Biosynthesis and Signal Transduction of Plant Growth Regulators and Their Effects on Bioactive Compound Production in Salvia miltiorrhiza (Danshen)","volume":"19","author":"Li","year":"2024","journal-title":"Chin. Med."},{"key":"ref_5","first-page":"69","article-title":"Dalmatian Sage (Salvia Officinalis L.): A Review of Biochemical Contents, Medical Properties and Genetic Diversity","volume":"80","author":"Liber","year":"2015","journal-title":"Agric. Conspec. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.phytochem.2014.12.026","article-title":"Carnosic Acid","volume":"115","author":"Dussort","year":"2015","journal-title":"Phytochemistry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/ffj.1875","article-title":"Factors Affecting Secondary Metabolite Production in Plants: Volatile Components and Essential Oils","volume":"23","author":"Figueiredo","year":"2008","journal-title":"Flavour. Fragr. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1055\/a-1453-0964","article-title":"White Sage (Salvia apiana)\u2013a Ritual and Medicinal Plant of the Chaparral: Plant Characteristics in Comparison with Other Salvia Species","volume":"88","author":"Krol","year":"2022","journal-title":"Planta Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.33320\/maced.pharm.bull.2015.61.01.004","article-title":"Essential Oil Composition of Salvia fruticosa Mill","volume":"61","author":"Cvetkovikj","year":"2015","journal-title":"Populations from Balkan Peninsula. Maced. Pharm. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1759-6831.2010.00070.x","article-title":"Distribution of Tanshinones in the Genus Salvia (Family Lamiaceae) from China and Its Systematic Significance","volume":"48","author":"Li","year":"2010","journal-title":"J. Syst. Evol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jiang, Z., Gao, W., and Huang, L. (2019). Tanshinones, Critical Pharmacological Components in Salvia miltiorrhiza. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00202"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dougu\u00e9 Kentsop, R.A., Devi, P., Copetta, A., Ruffoni, B., Parisi, V., Bisio, A., and Iobbi, V. (2024). Salvia Species: Biotechnological Strategies Applied to In Vitro Cultures for the Controlled Production of Bioactive Diterpenoids. Agronomy, 14.","DOI":"10.3390\/agronomy14040835"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10529-013-1350-z","article-title":"Sage in Vitro Cultures: A Promising Tool for the Production of Bioactive Terpenes and Phenolic Substances","volume":"36","author":"Marchev","year":"2014","journal-title":"Biotechnol. Lett."},{"key":"ref_14","unstructured":"Georgiev, V., and Pavlov, A. (2018). Biosynthesis of Salvia Specialized and Biotechnological to Increase Their Production. Salvia Biotechnology, Springer International Publishing."},{"key":"ref_15","unstructured":"Ramawat, K., Ekiert, H., and Goyal, S. (2019). Biosynthesis of Biological Active Abietane Diterpenoids in Transformed Root Cultures of Salvia Species. Plant Cell and Tissue Differentiation and Secondary Metabolites, Springer International Publishing."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hussain, M.J., Abbas, Y., Nazli, N., Fatima, S., Drouet, S., Hano, C., and Abbasi, B.H. (2022). Root Cultures, a Boon for the Production of Valuable Compounds: A Comparative Review. Plants, 11.","DOI":"10.3390\/plants11030439"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Krol, A., Kokotkiewicz, A., Gorniak, M., Naczk, A.M., Zabiegala, B., Gebalski, J., Graczyk, F., Zaluski, D., Bucinski, A., and Luczkiewicz, M. (2023). Evaluation of the Yield, Chemical Composition and Biological Properties of Essential Oil from Bioreactor-Grown Cultures of Salvia apiana Microshoots. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-33950-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1139\/b72-026","article-title":"Medium and Techniques for Induction and Growth of Monocotyledonous and Dicotyledonous Plant Cell Cultures","volume":"50","author":"Schenk","year":"1972","journal-title":"Can. J. Bot."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11738-015-1804-0","article-title":"Production of Essential Oils from in Vitro Cultures of Caryopteris Species and Comparison of Their Concentrations with in Vivo Plants","volume":"37","author":"Luczkiewicz","year":"2015","journal-title":"Acta Physiol. Plant"},{"key":"ref_20","first-page":"369","article-title":"Wild Type Root Cultures of Scutellaria Barbata","volume":"4","author":"Majdan","year":"2011","journal-title":"BioTechnologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1021\/np50078a014","article-title":"Tanshinone Production in Adventitious Roots and Regenerates of Salvia miltiorrhiza","volume":"54","author":"Shimomura","year":"1991","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s11240-005-9018-6","article-title":"Diterpenoids and Triterpenoids in Hairy Roots of Salvia sclarea","volume":"84","author":"Skrzypek","year":"2006","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kentsop, R.A.D., Iobbi, V., Donadio, G., Ruffoni, B., De Tommasi, N., and Bisio, A. (2021). Abietane Diterpenoids from the Hairy Roots of Salvia corrugata. Molecules, 26.","DOI":"10.3390\/molecules26175144"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0031-9422(00)95156-2","article-title":"Diterpenoid Production in Hairy Root Cultures of Salvia miltiorrhiza","volume":"32","author":"Hu","year":"1993","journal-title":"Phytochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1515\/znc-2006-5-609","article-title":"Establishment of Salvia officinalis L. Hairy Root Cultures for the Production of Rosmarinic Acid","volume":"61","author":"Grzegorczyk","year":"2006","journal-title":"Z. Fur Naturforschung Sect. C J. Biosci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Khoshsokhan, F., Babalar, M., Salami, S.A., Sheikhakbari-Mehr, R., and Mirjalili, M.H. (2022). Rosmarinic Acid Production in Hairy Root Cultures of Salvia nemorosa L. (Lamiaceae). Biocatal. Agric. Biotechnol., 45.","DOI":"10.1016\/j.bcab.2022.102494"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11240-021-02170-8","article-title":"Elicitor-Induced Phenolic Acids Accumulation in Salvia virgata Jacq. Hairy Root Cultures","volume":"148","author":"Abrishamchi","year":"2022","journal-title":"Plant Cell Tissue Organ Cult. (PCTOC)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.indcrop.2013.08.031","article-title":"Propagation of Salvia miltiorrhiza from Hairy Root Explants via Somatic Embryogenesis and Tanshinone Content in Obtained Plants","volume":"50","author":"Wang","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_29","first-page":"904","article-title":"Genetic Transformation of Salvia austriaca by Agrobacterium Rhizogenes and Diterpenoid Isolation","volume":"66","author":"Kisiel","year":"2011","journal-title":"Pharmazie"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s11627-001-0120-0","article-title":"Use of Ri-Mediated Transformation for Production of Transgenic Plants","volume":"37","author":"Christey","year":"2001","journal-title":"Vitr. Cell. Dev. Biol. Plant"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jbiotec.2020.05.002","article-title":"Establishment of Hairy Root Cultures of Salvia bulleyana Diels for Production of Polyphenolic Compounds","volume":"318","author":"Wojciechowska","year":"2020","journal-title":"J. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/sj.jim.2900624","article-title":"Production of Lithospermic Acid B and Rosmarinic Acid in Hairy Root Cultures of Salvia miltiorrhiza","volume":"22","author":"Chen","year":"1999","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hu, J., Wang, F., Liang, F., Wu, Z., Jiang, R., Li, J., Chen, J., Qiu, S., Wang, J., and Zhang, Y. (2022). Identification of Abietane-Type Diterpenoids and Phenolic Acids Biosynthesis Genes in Salvia apiana Jepson Through Full-Length Transcriptomic and Metabolomic Profiling. Front. Plant Sci., 13.","DOI":"10.3389\/fpls.2022.919025"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17","DOI":"10.5586\/asbp.2005.003","article-title":"In Vitro Cultures of Salvia officinalis L. As a Source of Antioxidant Compounds","volume":"74","author":"Grzegorczyk","year":"2005","journal-title":"Acta Soc. Bot. Pol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/s002990050763","article-title":"Carnosic Acid in Green Callus and Regenerated Shoots of Rosmarinus Officinalis","volume":"19","author":"Caruso","year":"2000","journal-title":"Plant Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Appiah, K.S., Mardani, H.K., Omari, R.A., Eziah, V.Y., Ofosu-Anim, J., Onwona-Agyeman, S., Amoatey, C.A., Kawada, K., Katsura, K., and Oikawa, Y. (2018). Involvement of Carnosic Acid in the Phytotoxicity of Rosmarinus Officinalis Leaves. Toxins, 10.","DOI":"10.3390\/toxins10120498"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1021\/jf0300745","article-title":"Phenolic Diterpenes, Flavones, and Rosmarinic Acid Distribution during the Development of Leaves, Flowers, Stems, and Roots of Rosmarinus Officinalis. Antioxidant Activity","volume":"51","author":"Lorente","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1080\/10826076.2013.807466","article-title":"Simultaneous Determination of Rosmarinic Acid, Salvianolic Acid B and Caffeic Acid in Salvia leriifolia Benth. Root, Leaf and Callus Extracts Using a High-Performance Liquid Chromatography with Diode-Array Detection Technique","volume":"37","author":"Modarres","year":"2014","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.indcrop.2010.05.009","article-title":"Bioactive Components of the Roots of Salvia miltiorrhizae: Changes Related to Harvest Time and Germplasm Line","volume":"32","author":"He","year":"2010","journal-title":"Ind. Crops Prod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.indcrop.2015.03.081","article-title":"Expression Profiles of Rosmarinic Acid Biosynthesis Genes in Two Salvia miltiorrhiza Lines with Differing Water-Soluble Phenolic Contents","volume":"71","author":"Song","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Grzegorczyk-Karolak, I., Krzemi\u0144ska, M., Kiss, A.K., Olszewska, M.A., and Owczarek, A. (2020). Phytochemical Profile and Antioxidant Activity of Aerial and Underground Parts of Salvia bulleyana Diels. Plants. Metab., 10.","DOI":"10.3390\/metabo10120497"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.indcrop.2018.11.027","article-title":"Phenolic Profiling and in Vitro Biological Properties of Two Lamiaceae Species (Salvia modesta and Thymus argaeus): A Comprehensive Evaluation","volume":"128","author":"Zengin","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Afonso, A.F., Pereira, O.R., Fernandes, \u00c2., Calhelha, R.C., Silva, A.M.S., Ferreira, I.C.F.R., and Cardoso, S.M. (2019). Phytochemical Composition and Bioactive Effects of Salvia africana, Salvia officinalis \u2018Icterina\u2019 and Salvia mexicana Aqueous Extracts. Molecules, 24.","DOI":"10.3390\/molecules24234327"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Afonso, A.F., Pereira, O.R., Fernandes, \u00c2.S.F., Calhelha, R.C., Silva, A.M.S., Ferreira, I.C.F.R., and Cardoso, S.M. (2019). The Health-Benefits and Phytochemical Profile of Salvia Apiana and Salvia Farinacea Var. Victoria Blue Decoctions. Antioxidants, 8.","DOI":"10.3390\/antiox8080241"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1055\/a-1272-2903","article-title":"Application of UHPLC-ESI-QTOF-MS in Phytochemical Profiling of Sage (Salvia officinalis) and Rosemary (Rosmarinus officinalis)","volume":"7","author":"Velamuri","year":"2020","journal-title":"Planta Medica Int. Open"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/0031-9422(92)83130-Q","article-title":"Diterpenes and Diterpene Quinones from the Roots of Salvia apiana","volume":"31","author":"Aguiar","year":"1992","journal-title":"Phytochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, F., Bao, Y., Yang, F., Yuan, L., Han, X., Huang, Y., Wei, Y., Zhang, L., Yang, Z., and Yang, D. (2024). Content Determination and Chemical Clustering Analysis of Tanshinone and Salvianolic Acid in Salvia spp.. Metabolites, 14.","DOI":"10.3390\/metabo14080441"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhang, C., Yang, D., Liang, Z., Liu, J., Yan, K., Zhu, Y., and Yang, S. (2019). Climatic Factors Control the Geospatial Distribution of Active Ingredients in Salvia miltiorrhiza Bunge in China. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-36729-x"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5511\/plantbiotechnology1984.13.69","article-title":"Rosmarinic Acid and Related Phenolics in Adventitious Root Cultures of Ocimum basilicum L.","volume":"13","author":"Tada","year":"1996","journal-title":"Plant Tissue Cult. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1080\/14786419.2015.1120725","article-title":"Micropropagation of Salvia Wagneriana Polak and Hairy Root Cultures with Rosmarinic Acid Production","volume":"30","author":"Ruffoni","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1021\/acs.jafc.5b04697","article-title":"Enhanced Diterpene Tanshinone Accumulation and Bioactivity of Transgenic Salvia miltiorrhiza Hairy Roots by Pathway Engineering","volume":"64","author":"Shi","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7473","DOI":"10.3390\/molecules18077473","article-title":"Effects of Combined Elicitors on Tanshinone Metabolic Profiling and SmCPS Expression in Salvia miltiorrhiza Hairy Root Cultures","volume":"18","author":"Cheng","year":"2013","journal-title":"Molecules"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Contreras, A., Leroy, B., Mariage, P.A., and Wattiez, R. (2019). Proteomic Analysis Reveals Novel Insights into Tanshinones Biosynthesis in Salvia miltiorrhiza Hairy Roots. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42164-3"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/0972060X.2021.1921622","article-title":"Chemical Composition and Antioxidant Activity of Root Essential Oil of Different Salvia leriifolia Populations","volume":"24","author":"Sarhadi","year":"2021","journal-title":"J. Essent. Oil Bear. Plants"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Khojasteh, A., Mirjalili, M.H., Alcalde, M.A., Cusido, R.M., Eibl, R., and Palazon, J. (2020). Powerful Plant Antioxidants: A New Biosustainable Approach to the Production of Rosmarinic Acid. Antioxidants, 9.","DOI":"10.3390\/antiox9121273"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3109\/07388551.2011.596804","article-title":"Rosmarinic Acid and Its Derivatives: Biotechnology and Applications","volume":"32","author":"Bulgakov","year":"2012","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_57","first-page":"443","article-title":"Critical Reviews in Biotechnology Green (Cell) Factories for Advanced Production of Plant Secondary Metabolites","volume":"40","author":"Marchev","year":"2020","journal-title":"Biotechnology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.tifs.2021.03.015","article-title":"Rosmarinic Acid\u2014From Bench to Valuable Applications in Food Industry","volume":"117","author":"Marchev","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143","DOI":"10.5010\/JPB.2019.46.3.143","article-title":"Adventitious Root Culture for Secondary Metabolite Production in Medicinal Plants: A Review","volume":"46","author":"Rahmat","year":"2019","journal-title":"J. Plant Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1104\/pp.125.2.1094","article-title":"Subcellular Compartmentation of the Diterpene Carnosic Acid and Its Derivatives in the Leaves of Rosemary","volume":"125","author":"Alegre","year":"2001","journal-title":"Plant Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1023\/A:1022806420209","article-title":"Growth and Rosmarinic Acid Accumulation in Callus, Cell Suspension, and Root Cultures of Wild Salvia fruticosa","volume":"73","author":"Karam","year":"2003","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sarropoulou, V., Paloukopoulou, C., Karioti, A., Maloupa, E., and Grigoriadou, K. (2023). Rosmarinic Acid Production from Origanum dictamnus L. Root Liquid Cultures In Vitro. Plants, 12.","DOI":"10.3390\/plants12020299"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s00299-004-0815-x","article-title":"Growth and Terpenoid Indole Alkaloid Production in Catharanthus Roseus Hairy Root Clones in Relation to Left- and Right-Termini-Linked Ri T-DNA Gene Integration","volume":"23","author":"Batra","year":"2004","journal-title":"Plant Cell Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00709-015-0790-9","article-title":"Establishment of Salvia castanea Diels f. Tomentosa Stib. Hairy Root Cultures and the Promotion of Tanshinone Accumulation and Gene Expression with Ag+, Methyl Jasmonate, and Yeast Extract Elicitation","volume":"253","author":"Li","year":"2016","journal-title":"Protoplasma"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jbiotec.2005.04.020","article-title":"Efficient Production and Recovery of Diterpenoid Tanshinones in Salvia miltiorrhiza Hairy Root Cultures with in Situ Adsorption, Elicitation and Semi-Continuous Operation","volume":"119","author":"Yan","year":"2005","journal-title":"J. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pavlov, A., and Bley, T. (2018). Bioreactor Technology for Hairy Roots Cultivation. Bioprocessing of Plant In Vitro Systems, Springer International Publishing AG.","DOI":"10.1007\/978-3-319-54600-1"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/10826068.2016.1168745","article-title":"The Production and Antiprotozoal Activity of Abietane Diterpenes in Salvia Austriaca Hairy Roots Grown in Shake Flasks and Bioreactor","volume":"47","author":"Kaiser","year":"2017","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s10529-013-1426-9","article-title":"Production of Tropane Alkaloids in Hyoscyamus Niger (Black Henbane) Hairy Roots Grown in Bubble-Column and Spray Bioreactors","volume":"36","author":"Jaremicz","year":"2014","journal-title":"Biotechnol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5586\/asbp.2010.001","article-title":"Antioxidant Compounds in Salvia officinalis L. Shoot and Hairy Root Cultures in the Nutrient Sprinkle Bioreactor","volume":"79","author":"Grzegorczyk","year":"2011","journal-title":"Acta Soc. Bot. Pol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BA20070103","article-title":"Growth of Hairy-Root Cultures in Various Bioreactors for the Production of Secondary Metabolites","volume":"49","author":"Mishra","year":"2008","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Mirmazloum, I., Slavov, A.K., and Marchev, A.S. (2024). The Untapped Potential of Hairy Root Cultures and Their Multiple Applications. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202410.1240.v1"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.biotechadv.2011.11.004","article-title":"Production of Biomass and Useful Compounds from Adventitious Roots of High-Value Added Medicinal Plants Using Bioreactor","volume":"30","author":"Baque","year":"2012","journal-title":"Biotechnol. Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1023\/A:1007627509824","article-title":"Isolation of High Quality DNA and RNA from Leaves of the Carnivorous Plant Drosera rotundifolia","volume":"17","author":"Bekesiova","year":"1999","journal-title":"Plant Mol. Biol. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jbiotec.2017.02.007","article-title":"Schisandra Lignans Production Regulated by Different Bioreactor Type","volume":"247","author":"Szopa","year":"2017","journal-title":"J. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Nadeem, M., Imran, M., Aslam Gondal, T., Imran, A., Shahbaz, M., Muhammad Amir, R., Wasim Sajid, M., Batool Qaisrani, T., Atif, M., and Hussain, G. (2019). Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review. Appl. Sci., 9.","DOI":"10.3390\/app9153139"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3138\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:04:40Z","timestamp":1760029480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":75,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073138"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073138","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]}}}